Sumatriptan Canon, 50 mg 10 pcs

Pharmacodynamics

Sumatriptan is a selective agonist of vascular 5-hydroxytrypta-min-1 receptors (5-HT1D) and does not act on other 5-HT receptor subtypes (5-HT2-5-HT7). 5-HT1D receptors are located mainly in the cranial blood vessels of the brain, and their stimulation leads to narrowing of these vessels.

In animals, sumatriptan selectively acts on vasoconstriction of carotid artery branches without affecting blood flow in cerebral vessels. The carotid artery vascular basin supplies blood to extracranial and intracranial tissues (including meningeal membranes), it is believed that dilation of cerebral membrane vessels and/or their edema is the main mechanism of migraine development in humans.

In addition, experimental evidence suggests that sumatriptan reduces trigeminal nerve sensitivity. Both of these effects may underlie the antimigraine action of sumatriptan.

Sumatriptan has demonstrated efficacy in the treatment of migraine attacks, including menstrual-associated migraine.

The onset of action is 30 min after an oral dose of 100 mg. Although the recommended oral dose is 50 mg, migraine attacks vary in severity from patient to patient. Doses of 25 mg to 100 mg have shown greater efficacy than placebo in clinical trials, but the 25 mg dose is statistically significantly less effective than 50 mg and 100 mg.

Pharmacokinetics

Migraine attacks have no significant effect on the pharmacokinetics of sumatriptan taken orally.

Introduction

After oral administration, it is rapidly absorbed, after 45 min its plasma concentration reaches 70% of the maximum level. The average value of absolute bioavailability is 14%, partly due to presystemic metabolism, partly due to incomplete absorption. The mean value of maximum plasma concentration (TCmax) after oral administration of 100 mg is 54 ng/ml.

Distribution

The binding to plasma proteins is 14-21%, the mean total distribution volume is 170L.

Metabolism

The main metabolite, the indoleukasic analog of sumatriptan, is excreted primarily with the urine, as free acid and glucuronide conjugate. This metabolite has no activity against 5-HT1- and 5-HT2-serotonin receptors.

Secondary metabolites of sumatriptan have not been detected.

Elimination

The elimination half-life (T1/2) is approximately – 2 h. Mean total plasma clearance is 1160 ml/min; mean renal clearance is 260 ml/min; extrarenal clearance is about 80% of total clearance.

Sumatriptan is metabolized by monoamine oxidase A.

Pharmacokinetics in patients in special groups

In patients with impaired hepatic function, the bioavailability of the drug may be significantly increased due to increased plasma concentrations of sumatriptan as a result of decreased presystemic clearance.

The effect of moderate hepatic impairment (Child-Pugh class B) on the pharmacokinetics of sumatriptan when administered subcutaneously has been evaluated. No significant differences were found in the subcutaneous pharmacokinetics of sumatriptan in patients with moderate hepatic impairment compared to healthy control patients.

Indications

Active ingredient

Composition

1 film-coated tablet, 50 mg contains:

active ingredient: sumatriptan succinate 70.00 mg, in terms of sumatriptan 50.00 mg;

excipients: Hyprolose (hydroxypropylcellulose Clucel LF) 4.00 mg, calcium hydrophosphate dihydrate 44.00 mg, croscarmellose sodium 3.00 mg, magnesium stearate 2.00 mg, mannitol 48.96 mg, calcium stearate 1.04 mg, microcrystalline cellulose 27.00 mg;

film coating composition: AQ-02003 Celoate 7.00 mg, including: [hypromellose (hydroxypropyl methylcellulose) 4.2 mg, macrogol (polyethylene glycol 6000) 1.4 mg, titanium dioxide 1.4 mg].

How to take, the dosage

Sumatriptan Canon should not be prescribed as a prophylactic. The recommended dose should not be exceeded.

The use of Sumatriptan Canon is recommended immediately at the first signs of a migraine attack, and Sumatriptan Canon is equally effective at any stage of a migraine attack.

The drug is taken orally by swallowing the whole tablet with water.

Adults

The recommended dose is 50 mg (1 tablet). Some patients may need a dose of 100 mg.

If a migraine attack does not resolve after the first dose, a second dose of the drug should not be prescribed to resolve the same migraine attack. In such cases, paracetamol, acetylsalicylic acid or non-steroidal anti-inflammatory drugs may be used to control the attack.

Sumatriptan Canon can, however, be used to control subsequent migraine attacks.

If a patient felt improvement after the first dose of the drug and then symptoms resumed, a second dose may be taken, provided that there is at least a 2-hour interval between doses, and no more than 300 mg is taken over a 24-hour period.

Sumatriptan can be used no sooner than 24 hours after taking ergotamine-containing medications; conversely, ergotamine-containing medications can be used no sooner than 6 hours after taking sumatriptan.

Particular patient groups

Children and adolescents (less than 18 years of age)

Efficacy and safety have not been demonstrated in this patient group.

Elderly patients (over 65 years of age)

Limited experience with sumatriptan in patients over 65 years of age. Pharmacokinetics in patients in this population are not significantly different from those in younger patients, but until additional clinical data are available, the use of sumatriptan in patients over 65 years is not recommended.

Interaction

No interaction of sumatriptan with propranololol, flunarizine, pisotifene and ethyl alcohol has been observed in healthy volunteers.

Long-term vasospasm was noted when concomitantly taken with ergotamine.

There are limited data on the interaction of sumatriptan with drugs containing ergotamine or other 5-HT1 receptor triptans/agonists. It is theoretically possible to increase the risk of coronary vasospasm, and co-administration of these drugs is contraindicated (see section “Contraindications”).

The period of time between the use of sumatriptan and ergotamine-containing drugs or another 5-NT1 receptor triptan/agonist is unknown. It will depend, among other things, on the dose and type of medication administered. The action may be additive in nature.

We recommend waiting at least 24 hours after administration of ergotamine or other 5-NT1 receptor tryptan/agonist drugs before using sumatriptan. Conversely, it is recommended to wait at least 6 hours after using sumatriptan before using ergotamine-containing drugs and at least 24 hours before using another tryptan/5-NT1 receptor agonist.

Possible interactions between sumatriptan and MAO inhibitors are contraindicated (see Contraindications).

There have been rare reports of the development of serotonin syndrome (including mental disorders, autonomic lability, and neuromuscular disorders) as a result of concomitant use of selective serotonin reuptake inhibitors (SSRIs) and sumatriptan.

The development of serotonin syndrome has also been reported with concomitant use of triptans with selective serotonin and noradrenaline reuptake inhibitors (SSRIs).

Special Instructions

The drug should be prescribed only if the diagnosis of migraine is beyond doubt.

The drug is contraindicated for use in hemiplegic, basilar and ophthalmoplegic forms of migraine.

Before starting treatment, the types of potentially dangerous neurological pathology (e.g., stroke, transient ischemic attacks) must be excluded if atypical symptoms are present or if the patient has not been diagnosed with a condition requiring the use of the drug.

Transient symptoms may occur after taking the drug, including chest pain and tightness that may be intense and extend to the neck area. If there is reason to believe that these symptoms are a manifestation of CHD, appropriate diagnostic testing should be performed.

The drug should not be used in patients with risk factors for CHD, including heavy smokers or users of nicotine replacement therapy, without prior cardiovascular evaluation.

Particular attention should be paid to postmenopausal women and men over 40 years of age with these risk factors. However, the screening does not always identify every patient with a heart condition.

In very rare cases, serious adverse cardiovascular events may occur in patients with no history of cardiovascular disease.

The drug should be used with caution in patients with controlled arterial hypertension, because transient increase of blood pressure and peripheral vascular resistance have been observed in a small number of patients.

There have been rare post-registration reports of the development of serotonin syndrome (including mental status disorder, autonomic lability, and neuromuscular disorders) resulting from concomitant use of selective serotonin reuptake inhibitors (SSRIs) and sumatriptan.

The development of serotonin syndrome has also been reported with concomitant use of triptans and selective norepinephrine reuptake inhibitors (SSRIs). In case of concomitant use of drugs from the group of SSRIs and/or SSRIs, the patient’s condition should be closely monitored.

The concomitant use of any triptan (5-NT1 agonist) with sumatriptan is not recommended.

Sumatriptan should be used with caution in patients in whom absorption, metabolism, or excretion of sumatriptan may be significantly altered, such as patients with hepatic insufficiency or impaired renal function (Child-Pugh class A or B).

Sumatriptan should be used with caution in patients with a history of seizures or other risk factors for decreased seizure threshold, as seizures have been reported with sumatriptan.

In patients with hypersensitivity to sulfonamides, an increased risk of allergic reactions (from skin manifestations to anaphylactic shock) has been noted when administering sumatriptan. There are limited data on cross-sensitivity, so caution should be exercised before using sumatriptan in these patients.

Unwanted reactions may occur more frequently during concomitant use of triptans and herbal preparations containing St. John’s Wort (Hypericum perforatum).

The abuse of medications intended to relieve acute headache has been associated with worsening headaches in sensitive patients (medication abuse-related headache). In this case, the possibility of withdrawal of the drug should be considered.

The effect on the ability to drive and operate vehicles

Migraine patients may experience somnolence associated both with the disease itself and with the use of the drug. Caution should be exercised when driving motor vehicles and operating moving machinery during treatment.

Contraindications

Hypersensitivity to any of the ingredients of the drug.

Hemiplegic, basilar or ophthalmoplegic forms of migraine.

Coronary heart disease (CHD), (including suspected), angina pectoris (including Prinzmetal angina), myocardial infarction (includinghistory), postinfarction cardiosclerosis, and symptoms suggestive of coronary heart disease.

Moderate to severe arterial hypertension, and uncontrolled mild arterial hypertension.

Occlusive diseases of peripheral arteries.

Stroke or transient ischemic attack (including history).

Severe hepatic and/or renal dysfunction.

Concurrent use with ergotamine or its derivatives (including methysergide) or other tryptamines / 5-HT1 receptor agonists.

Use while taking monoamine oxidase inhibitors (MAOIs) or earlier than 2 weeks after withdrawal of these drugs.

Arterial hypertension (controlled).

Diseases in which absorption, metabolism or excretion of sumatriptan may be altered (e.g., impaired renal or hepatic function).

Hypersensitivity to sulfonamides (administration of sumatriptan may cause allergic reactions, with severity ranging from skin manifestations to anaphylaxis). Data on cross-sensitivity are limited, but caution should be exercised when administering sumatriptan to such patients.

Side effects

The undesirable reactions presented below are listed according to organ involvement and frequency of occurrence. The frequency is defined as follows:

Very common (≥1/10), common (≥1/100 and <1/10), infrequent (≥1/1000 and <1/100), rare (≥1/10000 and <1/1000), very rare (<1/10000), unknown (frequency cannot be estimated from available data).

Clinical study data

Nervous system disorders:

often dizziness, somnolence, sensory disturbances, including paresthesias and decreased sensitivity.

Vascular disorders:

often – transient increase in blood pressure (observed soon after taking the drug), hot flashes.

Respiratory system, chest and mediastinum disorders:

often – dyspnea.

Gastrointestinal disorders:

often – nausea, vomiting (causal relationship of adverse reactions with taking the drug is not proven).

Muscular and connective tissue disorders:

often – a feeling of heaviness (usually transient, can be intense and occur in any part of the body, including the chest and throat).

General disorders and disorders at the site of administration:

often, pain, feeling of cold or heat, feeling of pressure or tightness (usually transient, may be intense and occur in any part of the body, including the chest and throat), weakness, fatigue (usually mild to moderate, transient).

Laboratory and instrumental findings:

very rarely, minor abnormalities in hepatic test values.

Post-registration data

Immune system disorders:

frequency unknown – hypersensitivity reactions, including skin manifestations, as well as anaphylaxis.

Nervous system disorders:

frequency unknown – seizures (in some cases observed in patients with a history of seizures or concurrent conditions predisposing to the occurrence of seizures; no risk factors were identified in some patients), tremor, dystonia, nystagmus, scotoma.

Mental disorders:

frequency unknown-anxiety.

Visual disorders:

frequency unknown – flickering, diplopia, decreased visual acuity, blindness (usually transient). However, visual disturbances may be due to the migraine attack itself.

Chronic disorders:

Prevalence unknown – bradycardia, tachycardia, palpitations, arrhythmias, signs of transient myocardial ischemia on ECG, coronary vasospasm, angina, myocardial infarction.

Vascular disorders:

frequency unknown – arterial hypotension, Raynaud’s syndrome.

Gastrointestinal disorders:

frequency unknown – ischemic colitis, diarrhea.

Musculoskeletal and connective tissue disorders:

frequency unknown – neck stiffness, arthralgia.

Skin and subcutaneous tissue disorders:

frequency unknown – hyperhidrosis.

Overdose

Symptoms

No adverse reactions other than those listed above under “adverse effects” are observed when taken orally up to 400 mg.

Treatment

In case of sumatriptan overdose, patients should be monitored for at least 10 h and symptomatic therapy should be given if necessary. There are no data on the effect of hemodialysis or peritoneal dialysis on the plasma concentration of sumatriptan.

Pregnancy use

Pregnancy

The use of sumatriptan in pregnancy is possible only if the expected benefit to the mother outweighs the possible risk to the fetus.

The data from the use of sumatriptan in more than 1,000 women in the first trimester of pregnancy do not contain sufficient information to draw definitive conclusions about the risk of fetal birth defects; experience with sumatriptan in the second and third trimesters of pregnancy is also limited.

The results of preclinical studies in animals have not shown a direct teratogenic effect of sumatriptan on the fetus or a negative effect on prenatal and postnatal embryonic or fetal development in rats. However, there is evidence of an effect of sumatriptan on embryonic and fetal viability in rabbits.

Breastfeeding

Sumatriptan has been shown to be excreted into breast milk following subcutaneous administration. Breastfeeding should be discontinued while sumatriptan is in use, and breastfeeding may not occur until 12 hours after taking the drug.

Similarities